Tumor is one of common diseases with high mortality in modern society. Conventional tumor treatment methods are mainly by surgical removal and preoperative and postoperative chemotherapy. However, the therapeutic effects of such methods are unsatisfactory. Targeted drugs have attracted much attention due to high specificity and low toxicity.
Studies in recent years indicate that the high expression of the epidermal growth factor (EGFR) is closely related to the occurrence, development and prognosis of tumors. Accordingly, targeted drugs specific for EGFR, including monoclonal antibodies (e.g., cetuximab, Matuzumab, etc.) and micromolecular tyrosine kinase inhibitors (e.g., gefitinib, erlotinib, lapatinib, etc.), have been successively developed and gradually applied in clinical practices for tumor treatment. Although EGFR inhibitors have achieved encouragingly therapeutic effects in clinical treatment of tumors because of their advantages of high selectivity and low toxicity, some of patients are insensitive to such treatment and some of patients eventually become resistant to such drugs.
In addition to EGFR, COX-2 is also regarded as a very promising target in tumor treatment. In recent years, it has been found from the studies both in China and at abroad that the expression of COX-2 obviously increases in many malignant tumor tissues. COX is a key enzyme in the synthesis process of prostaglandin. Cyclooxygenase-2 (COX-2), as an inducible enzyme, may be produced under the stimulation of many factors, playing an important role in the occurrence, development and spread of tumors. It mainly functions by suppressing the apoptosis, suppressing the anti-tumor function of the immune system, promoting the tumor angiogenesis, enhancing the invasiveness and other mechanisms.
Actually, there are many links between EGFR and the expression of COX-2. At present, some groups have proposed that the activation and over-expression of COX-2 is attributed to the activation of EGFR. EGFR is simulated by a ligand-amphiregulin (AR) thereof and thus induces the nucleus targeting of COX-2 in the polarized colonic epithelial cells, the release of PG and the subsequent mitosis. COX-2 inhibitors have showed that they can prevent a series of such behaviors.
Nonsteroidal anti-inflammatory drugs (NSAID), which are inhibitors of cyclooxygenase (COX), have been widely applied in clinic as anti-inflammatory, antipyretic and analgesic drugs. Some of such drugs, already as OTC drugs, may be directly obtained from drugstores without prescriptions. Clinical practices both in China and aboard over the years have indicated that NSAID anti-inflammatory and analgesic drugs can slow down the occurrence and development of a wide range of tumors. The studies of tumor treatment by NSAID anti-inflammatory and analgesic drugs mostly focus on colon cancer. It has been found from animal models, in-vitro pharmacological experiments, therapeutic tests or epidemiological surveys that NSAIDs can prevent the occurrence of colon cancer in the early stage.